30 Anand Upasani1, Divyesh Desai1, Imran Mushtaq1, and Pankaj Mishra2 1 Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK 2 Evelina London Children’s Hospital, Guy’s & St. Thomas’ Hospital, NHS Foundation Trust, King’s College Hospital, NHS Foundation Trust, London, UK There are many conditions that affect the genital organs, varying from minor conditions treated conservatively to those that cause significant long‐term functional, psychological, and emotional problems. A sound knowledge of the wide ranges conditions would ensure the essential counselling and initiation of treatment starts on the correct path. Keywords hypospadias; epispadias; urethral valves; posterior urethral valve (PUV); syringocele; urethral duplication; disorders of sex development (DSD) The prepuce develops at the same time as the urethra and is dependent on normal urethral development. At about eight weeks of gestation, low preputial folds appear on both sides of the penile shaft, which join dorsally to form a flat ridge at the proximal edge of the corona. The ridge does not entirely encircle the glans because it is blocked ventrally by incomplete development of the glanular urethra. Thus, the preputial fold is transported distally by active growth of the mesenchyme between it and the glanular lamella. The process continues until the preputial fold (foreskin) covers all of the glans. If the genital folds fail to fuse, the preputial tissues do not form ventrally; consequently, in hypospadias, preputial tissue is absent ventrally and is excessive dorsally [1, 2]. Phimosis is the most common urological presentation in children. It is either primary or physiological or secondary or pathological (e.g. Lichen sclerosis also commonly known as balanitis xerotica obliterans ([BXO]). The foreskin is physiologically non‐retractile beyond the glandular sulcus, in almost 100% of neonates, 50% by one year, and in most of the cases becomes retractile spontaneously [3–5]. The incidence drops to <10% at 7 years and around 1% of 18 year old have nonretractile foreskin [3–5]. In all neonates the inner foreskin skin is fused to the glans, and the separation occurs gradually due to accumulation of smegma. The smegma is the sebaceous secretion from the inner foreskin that accumulates between the skin and glans and causes its separation. The accumulating smegma can form pearl like cyst (i.e. smegmal cyst) under the foreskin, or some time mimics purulent discharge when expulsed out of foreskin meatus and often prompts urological consultation, needing only reassurance (Figure 30.1). Figure 30.1 Smegmal cyst. Given the natural history of phimosis in children, only symptomatic patients, particularly those with recurrent local infections or scarring should undergo surgery before puberty in the absence of foreskin abnormalities on physical examination [5]. In symptomatic patients, nonsurgical treatment can still be offered in the form of a course of four to eight weeks with one to two applications per day of topical steroids, with a success rate of >90%; however, there is a recurrence rate of 15–20% [4, 6–8]. Of note, it is controversial whether local steroids are more effective than preputial manipulation and stretching alone [5, 6]. In patients experiencing recurrent symptoms despite local steroids, circumcision is the standard treatment. If the patient or the parents wish the prepuce to be preserved, preputioplasty techniques (Figure 30.2), involving a one or more dorsal incisions and transverse suturing resulting in widening the preputial ring, are an option, although many surgeons consider the cosmetic results of these procedures unacceptable [9, 10]. Figure 30.2 Preputioplasty. Only the tight band need be incised. Afterwards the parent must keep the prepuce regularly reduced. The only absolute indications for a circumcisions are secondary phimosis (i.e. BXO), paraphimosis, recurrent infections with scarring, other indications include primary phimosis (i.e. patient preference usually cultural or religious reasons), recurrent balanoposthitis, and recurrent urinary tract infections (UTIs) in patients with urinary tract abnormalities (as this significantly reduces the bacterial colonisation of the glans) [4]. Circumcision is contraindicated in patients with an acute local infection and congenital penile anomalies where the foreskin will be needed for reconstruction (e.g. hypospadias or buried penis) [4]. Different treatment options like preputial stretching, preputioplasty, or topical corticosteroid creams have been proposed as alternative therapy as well. Circumcision may be performed with local or general anaesthesia. If local anaesthetic is used, it must not contain adrenaline because arterial spasm caused by adrenaline may lead to necrosis of the penis. Care must be taken in using the diathermy to avoid coagulation of the vessels of the penis. The bipolar diathermy is safe, but if this is not available, the penis should be surrounded by swabs soaked in saline to provide a wide pathway for the current to return to earth (Figure 30.3), however, the wide availability of bipolar diathermy as leads to the this risk is almost nonexistent. Figure 30.3 The hazards of diathermy in the penis are avoided by using the bipolar diathermy. Draw the foreskin forwards. Make a clean incision with a knife level with the corona of the glans (Figure 30.4). Then draw the foreskin backwards, if necessary making a small slit in the prepuce. Make a second clean incision with the knife 3–4 mm proximal to the sulcus of the glans. Join the two incisions and dissect the sleeve of skin off the shaft of the penis. Seal every small vessel with the bipolar diathermy or very fine catgut. Figure 30.4 Technique of circumcision. If the frenulum is prominent and short then it could be divided with bipolar forceps. Use only very fine absorbable sutures and or tissue glue as per the preference. Circumcision can be associated with severe complications, such as glanular amputation or urethral fistula formation, if the procedure is performed by physicians not properly trained [11]. In hospital setting, complications after elective circumcision are reportedly less than 1%. Acute complications are usually minor and most commonly involve bleeding, infection, or an imperfect cosmetic outcome. Late complications include trapped penis, skin bridges, and meatal stenosis [12]. Paraphimosis is defined by acute swelling and inflammation of the distal penis and glans caused by a constriction ring of tight foreskin. Paraphimosis is a medical emergency because delay in treatment can cause maceration of foreskin and even glanular ischemia [4, 13]. Most cases are amenable to reduction in accidents and emergencies with the use of topic anaesthetics, oral morphine, or intravenous injection sedation depending on the age of the patient. The manoeuvre used for reduction of an uncomplicated paraphimosis is performed by first squeezing the glans gently to reduce its volume and then, with the help of the index and middle fingers, the thumb is used to slowly push the glans proximally through the phimotic ring. Other substances or manoeuvres that have been used to help reduce glans swelling include sugar [14], mannitol soaked gauze [15], hyaluronidase [16], puncture of the prepuce with a small gauge needle [17], and an ice pack [18]. If conservative manoeuvres are not successful, dorsal slit or circumcision may be required; however, it might lead to unsatisfactory cosmetic outcomes, needing revision surgery later on [4]. Normal penile skin is susceptible to infections and inflammation. Nonspecific infections are most commonly caused by gram‐positive organisms (i.e. Staphylococcus pyogenes and Staphylococcus aureus), which are saprophytes of the skin. However, the causative organism is seldom identified, as swab cultures are generally not obtained [5]. The infection causes a collection of debris or pus under the foreskin that presents with swelling, erythema and inflammation. This is called balanitis (i.e. inflammation of glans) or balanoposthitis (i.e. inflammation of glans and foreskin). Balanoposthitis is seen in approximately 4% of uncircumcised boys, mostly between two and five years of age after potty training [19]. The aetiology is unclear, and no cause can be identified in many cases, although infection, mechanical trauma, contact irritation, and contact allergy are cited [20]. When the bacteria find skin or mucosal breakdown, they gain access to the subcutaneous tissue, resulting in diffuse cellulitis of the whole penis, which is sometimes quite dramatic. This may be associated with discharge, and patients may also complain of dysuria, bleeding from the foreskin, and glans ulceration [19]. In more severe cases, skin erythema can be accompanied by pain and fever. Treatment of balanoposthitis generally includes sitz baths and local antibiotic creams [21]. In cases of penile cellulitis or systemic symptoms, oral broad‐spectrum antibiotics should be administered. Short‐term bladder catheterization can be required in cases of acute urinary retention. Surgical procedures, such as incision and drainage, are almost never required, but recurrent infections can cause local scarring and phimosis requiring eventual circumcision [5]. The other possible diagnosis to be considered while assessing patients presenting with penile swelling, erythema, and inflammation caused by trauma, hair coil penile strangulation syndrome, animal attack, insect bite, bicycle accident, zipper injury, and electrical injury [22–27]. BXO is cause of pathological phimosis in paediatric population (Figure 30.5). BXO is a chronic progressive dermatitis of unknown aetiology, a variant of lichen sclerosus et. atrophicus confined to the male genitalia. In most cases, only the prepuce, but in some, the glans, external urethral meatus, and urethra may be involved as well. The incidence of the condition is unknown, but most authors agree it is increasing and many cases of phimosis undergoing nonelective circumcision in childhood might be in fact have undiagnosed BXO [5, 28]. However, BXO can be found in about 20% of cases with phimosis at <10 years of age [4]. It is diagnosed by histological features, including hyperkeratosis and hyperplasia of the squamous mucosa along with homogenous collagen deposition in the upper dermis [28]. Figure 30.5 Balanitis xerotica obliterans. Clinically, the condition can be suspected in the presence of a white, sclerotic, scared, nonretractile preputial ring. If the inflammatory process involves the external urethral meatus or urethra, meatal stenosis or urethral strictures can ensue. Most of the patients are asymptomatic. Progressive preputial tightening is the most common complaint [5]. Nonspecific voiding symptoms can be present, particularly if there is involvement of the external meatus or urethra [29]. In terms of treatment, circumcision alone is generally curative. Meatotomy or meatoplasty might be required in cases of meatal stenosis, whereas rare cases of urethral stricture make the condition very difficult to treat, requiring multiple urethral dilatation and might require substitution urethroplasty with oral mucosa [29, 30]. Adjuvant treatments with corticosteroids have also been proposed preoperatively, intraoperatively, or postoperatively, but the actual role of such an adjunctive treatment is unknown [29]. Surgery for BXO can be associated with quite a high complication rate. Meatal stenosis can recur after circumcision and the disease can progress leading to meatal stenosis or urethral stricture [5]. A buried penis refers to a normal‐sized penis buried in prepubic tissue. A normal penis can be buried by large scrotal masses, such as hernias or hydroceles or by the presence of excessive suprapubic fat. The prepubic fat can reduce in volume dramatically as the child learns to walk along with appropriate dietary advice and physical activity [5]. Some surgeons recommend that any surgery is deferred at least until the child is three years old [31]. The prepubic fat is sensitive to androgens, penile appearance can improve spontaneously as the child approaches puberty [32, 33]. Megaprepuce is indeed a variant of buried penis where there is a large redundancy of the inner preputial layer, characterised by a penis with a wide dome‐shaped base that exhibits hemispheric ballooning during micturition. There is an enormously capacious preputial sac, engulfing the whole penile shaft and upper scrotum (Figures 30.6 and 30.7). Urine collects in this preputial sac and dribbles more or less continuously. The sac can be readily emptied by compression [34]; this prompted the term ‘preputial bladder’. It has been widely debated whether such skin excess is congenital or acquired because of progressive stretching of the inner preputial mucosa during micturition in a phimotic prepuce [35]. Surgery is usually undertaken because of functional and cosmetic concerns and poses significant technical challenges. The limiting factors are the deficiency of penile shaft skin, an absence of defined penopubic and penoscrotal angles and a marked excess of inner preputial ‘mucosa’. Different surgical techniques have been described. Essentially, the excess inner preputial skin is excised. The penile skin is refashioned resulting in a circumcised penis. Postoperatively, redundant penile skin or recurrence of the buried appearance is not uncommon and revision surgery may be required [36, 37]. Figure 30.6 Congenital megaprepuce. Source: Courtesy Prof Sandesh Parelkar, KEM Hospital, Mumbai India. Figure 30.7 Congenital megaprepuce (filled with urine). Source: Courtesy Prof Sandesh Parelkar, KEM Hospital, Mumbai India. Hypospadias, by definition, implies that the urethral meatus is placed ventrally, short of its normal terminal location. It can be located anywhere from the under surface of the glans to the perineum. Embryologically, most of the urethra is formed by in‐rolling of the urethral folds of the developing phallus (which involves fusion of the medial edges of the endodermal urethral folds along with the ectodermal edges of the urethral groove that fuse to form the median raphe), but the last part – the channel through the glans – starts as a solid rod and then canalises. This process takes place between 8 to 12 weeks of gestation. The glanular urethra forms after the 16th week of gestation either by endodermal cellular differentiation or by primary intrusion of ectodermal tissue from the glans pit [38–40]. Any part of this complex process may go wrong. Its most severe forms are often associated with undescended testes and should raise the suspicion of disorder of sexual development (DSD). If the solid cord that burrows through the glans fails to canalise, the urethra opens on its ventral aspect – glandular hypospadias. This is common, and apart from looking slightly unusual, never causes any functional trouble (Figure 30.8). Figure 30.8 Degrees of hypospadias. Figure 30.9 (a, b, and c) Distal hypospadias. Source: Courtesy Prof Sandesh Parelkar, KEM Hospital, Mumbai India. Failure of enrolling of the urethral folds is accompanied by errors in development of the corpora cavernosa and spongiosum. The distal part of the corpus spongiosum may be a thin strand of fibrous tissue which acts like the cord of a bow causing the penis to bend over during erection – chordee. The incidence of hypospadias is 1 in 300–500 live male births [4, 41]. However, there is considerable regional variations worldwide. A variety of genetic, hormonal, enzymatic, and environmental factors have been implicated as possible etiological factors. Low birth weight and higher maternal age may also play a role (possibly mediated by placental insufficiency). Hypospadias is more common in monozygotic twins and in the offspring of fathers who have hypospadias, indicating that there may be a polygenic inheritance. Recently, hypospadias is associated with specific gene (Ins l3) knockout mice. The overall incidence of hypospadias in first‐degree male relatives of affected boys is 7–10%, rising to 10–20% in brothers of boys with severe forms of the condition [41]. Hypospadias is associated with high incidence of undescended testes. The average incidence is 5–10% but can rise as high as 50% is severe cases [41, 42]. There can be associated inguinal hernias or hydroceles. Abnormalities of the urinary tract are unusual and occur in approximately 2% of patients; thus, routine ultrasound of these children is unnecessary. Severe forms of hypospadias are also associated with a persistent prostatic utricle in 14–20% of cases, which on occasions can make urethral catheterisation of the bladder difficult [41, 42]. Routine investigations to identify a utricle are not recommended as most cases are asymptomatic. It is essential to exclude disorders of sexual development early on in patients with hypospadias with undescended testicles.The use of oral contraceptive pills during pregnancy increase the risk of hypospadias [4]. Commonly used anatomical classification of hypospadias (Figures 30.8–30.10): Figure 30.10 (a, b, and c) Proximal hypospadias with chordee. Source: Courtesy Prof Sandesh Parelkar, KEM Hospital, Mumbai India. It has three major components in various combinations: Overall there is hypoplasia of the ventral skin and spongiosum with resultant deficiency of tissues that give rise to a spectrum of presentations. Not all three of these features may be present in every case; hence, the management needs to be individualised. Therefore, can be grouped into: mild (i.e. distal or penile without chordee, micropenis, or scrotal anomalies) or severe (i.e. proximal and associated chordee and scrotal anomalies) [4]. Usually diagnosed at birth or when foreskin is retracted. Examination should include presence of other features of hypospadias, as well as presence of cryptorchidism and other congenital anomalies. Severe hypospadias with cryptorchidism or ambiguous genitalia will require a complete genetic and endocrine work‐up to exclude DSD. Indications for surgery include functional and cosmetic. Functional reasons include voiding (straight in standing position), sex, and reproduction. However, not all cases need treatment and management needs to be individualised rather than protocol driven. It is crucial to ensure appropriate parental counselling. Current practice is to aim for surgical correction in the preschool age preferably while the child is in nappies (6–18 months) [4, 43, 44]. More than 300 types of operations have been described in literature. It is beyond the scope of this book to go through the technical aspects in depth. However, the general principles are [45, 46]: Preoperative testosterone, dihydrotestosterone, or beta‐chorionic gonadotropin locally or parenterally can lead to a significant enlargement of the glans and shaft of the penis and is especially helpful with proximal hypospadias, small penises, small glans, or poor urethral plates [4]. Surgical tips include keeping the use of diathermy or tourniquet time to the minimum, attention to symmetry, tension free and wide calibre urethroplasty, adequate size meatus, and use of additional water‐proofing layer (Figure 30.11). Figure 30.11 Outcome of the foreskin graft for proximal hypospadias. Source: Courtesy Prof Sandesh Parelkar, KEM Hospital, Mumbai India. In the majority of cases (>70%), excision of the chordee connective tissue will straighten the curvature. However, if there is residual curvature, it will be due to corporeal disproportion and will require straightening with dorsal midline plications or a Nesbit plication [4]. In severe curvatures (>45°), which is also associated with a short urethral plate, a more extensive reconstructive operation will be required, but in essence, is comprised of ventral lengthening procedures and plications with and without flaps or grafts. Many procedures have been described; however, the type of operation depends mainly on the type of hypospadias: For distal hypospadias with minimal or no chordee and a good size glans tubularised incised plate urethroplasty [47] with or without a graft [48] is the most commonly performed procedure (i.e. Snodgrass‐Orkiszewski). In this operation the native urethral plate is tubularised by making two parallel incisions at the edge of urethral pate and a midline incision in the urethral plate is made (with or without free foreskin graft) to facilitate the tension‐free repair. The lateral edges of the parallel incisions are mobilised to raise glans wings and glansplaty is performed. Use of fine instruments, fine sutures, inversion of epithelium, using dartos flap as barrier layer over the urethroplasty, and a tension‐free repair is key to the good outcome (Figure 30.12). Figure 30.12 Postoperative outcome of single‐stage hypospadias repair. Source: Courtesy Prof Sandesh Parelkar, KEM Hospital, Mumbai India. The main complication of this type of hypospadias repair is breakdown of part of the suture line, resulting in a fistula. Several months should be allowed to pass before attempting to repair it. A meatal advancement and glansplasty (MAGPI) has also been described for selected cases of very distal hypospadias. Cut the little fold at the distal end of the pit which represents the true meatus in the midline and close it transversely (Figure 30.13). Make a second transverse incision just proximal to the urethra. Draw it up with a skin hook. Mobilise the prepuce on either side and swing it down beneath the glans to cover the raw area. The penis now looks as if circumcision has been performed. No catheter is needed as no urethroplasty has been done. This operation has gone out of use and should only be used in selected cases. Figure 30.13 Meatal advancement and glansplasty (MAGPI) operation. An onlay island flap from the prepuce or meatal‐based flaps (i.e. the Mathieu technique) can also be used for correction of distal hypospadias without chordee. Use of fine instruments, fine sutures, inversion of epithelium, using dartos flap as barrier layer over the urethroplasty, and a tension‐free repair is key to the good outcome. For those with significant chordee that persists after degloving of the penile shaft, selected penile or proximal hypospadias or a small glans, a two‐staged approach is preferred with preputial, buccal, or posterior auricular grafts. The first stage involves correction of chordee and lying open of the glans and putting the graft in to make a neourethral plate (Figure 30.14), which is tubularised in the second stage (Figures 30.15 and 30.16). The time interval between the two stages is six months. [49, 50] As shown previously, the foreskin could be brought ventrally either as a flap after incising it in midline or as a free‐graft (more popular). Figure 30.14 (a) Two‐stage hypospadias repair. First, the chordee is corrected and the meatus allowed to drop back. (b) The glans is slit open, (c) the foreskin is divided to form two thick flaps which are (d) brought round to cover the underside of the penis and (e) left to heal. Figure 30.15 At second stage, a full‐thickness skin tube is outlined and the skin closed over it to form a new urethra. Figure 30.16 The urethral plate marked for tubularisation at the second‐stage operation. Source: Courtesy Prof Sandesh Parelkar, KEM Hospital, Mumbai India. In the minor forms of hypospadias, like the granular hypospadias with hooded foreskin and no chordee, the surgery is mainly for the cosmetic reason, and there has to be a clear discussion about need and aim of surgery with family. If surgery is opted, then in most of the cases, a modified circumcision (i.e. involves partial degloving and rearrangement of foreskin to get rid of the dorsal hood) (Figure 30.17) or foreskin reconstruction is sufficient. Figure 30.17 Modified circumcision for minor forms of hypospadias. In almost all forms of hypospadias surgery, an 8‐Fr feeding tube is used as a urethral stent and soft compression dressing around the penis; both are removed after seven days. Early complications include haemorrhage, wound infection, and wound dehiscence. The rationale behind the use of compressive dressing is to reduce bleeding and hematoma formation, which may predispose to infection and wound dehiscence. Late complications are well known. The urethra‐cutaneous fistula can occur in up to 30% of the cases (Figure 30.18) [41]. Except for some of the very small fistulae in the immediate postoperative period most will require surgical closure. Prior to closure of a fistula, it is imperative to exclude meatal or distal urethral strictures to prevent recurrence. Figure 30.18 Postoperative subcoronal urethral fistula. Meatal stenosis is usually secondary to ischemia or inadequate mobilisation of the glans wings. It presents as spraying of urine, thin stream, dysuria, or urinary infections. It responds to meatal dilatation, but some cases need a formal meatotomy or meatoplasty. Urethral stricture, persistent chordee, BXO of the neourethra, and urethral diverticulum are other late complications that warrant surgical revision. In summary, despite advances in technique, instrumentation and aftercare, correction of hypospadias remains one of the most challenging conditions in paediatric urology. There is no place for the ‘occasional’ hypospadias surgeon, even in the correction of so‐called ‘minor’ hypospadias. Surgeons should have a detailed understanding of the various concepts, be well versed in a variety of surgical techniques, and have a sufficient clinical workload to obtain consistently good results. Epispadias is defined as presence of urethral meatus along the dorsal surface of the penis. It commonly occurs as a part of the bladder exstrophy‐epispadias complex (incidence 1 in 50 000). When is occurs by itself, it is known as primary epispadias and is relatively rare (incidence ~1 in 120 000 for males and ~1 in 400 000 in females) [51]. The caudal most aspect of the cloaca (phallic cloaca) extends distally through the developing genital tubercle. Failure of proliferation of rostral mesoderm of the genital tubercle and the caudal displacement of the cloaca results in epispadias [52]. There is variable diastasis which tends to be less severe than in bladder exstrophy. More often the pelvic ring is complete with an apparently normal abdominal wall [51]. In males, the urethra may open on the glans (i.e. glanular epispadias), on the shaft (i.e. penile epispadias), or proximally at the junction with the anterior abdominal wall (i.e. pubic or penopubic epispadias) (Figure 30.19a and b). Involvement of the bladder neck and resulting incontinence is seen in both penile and penopubic type. If there is diastasis, there will be a rotation and widening of the corpora cavernosa, with lateral neurovascular bundles. There might also be associated penile shortening. These may lead to subfertility. Figure 30.19 (a) Subcoronal primary epispadias. (b) Penopubic epispadias. While, in females the urethra is wide open on its dorsal surface, and the bifid clitoris lies on either sides. There is a poorly developed labia (Figure 30.20). Because of a short urethra and deficient bladder neck, incontinence is a rule in female epispadias. Figure 30.20 Primary epispadias in female child. In both sexes, there is a high risk (40–50%) of vesicoureteric reflux (VUR), which might require ureteric reimplantation. Prenatal diagnosis is rare. Severe forms are usually detected at birth due to abnormal appearance of the genitals. In boys, the less severe (glanular) forms the prepuce is intact and the condition may not become apparent until the prepuce becomes retractile or incidentally at the time of circumcision. In girls, the classical presentation is in childhood with a failure of potty training or a history of dribbling or stress incontinence. Surgical correction is commonly performed in the first year of life (Figure 30.21). Our procedure of choice is Kelly procedure [53] for all female epispadias and male epispadias with incompetent bladder neck mechanism as assessed on the cystoscopy. The main principals of Kelly procedure are: mobilising the corporal attachments along with the periostium from the symphysis pubis, dividing the pelvic floor muscular attachment from the pubic rami while preserving the pudendal neurovascular supply to penis, tubularisation and ventralisation of the urethra, wrapping the proximal urethra with freed‐up pelvic floor muscles, bladder neck reconstruction, and skin cover to penis. Figure 30.21 Outcome of isolated distal epispadias surgery. For the distal epispadias in boys with competent bladder neck, modified Cantwell–Ransley technique is sufficient for penile reconstruction [54]. The urethral plate is fully mobilised off the penile corpora from the proximal urinary outlet and corporeal bodies except at the glans. It is then tubularised and brought to a ventral position, and the corpora cavernosa are positioned dorsal to the urethra. A continent procedure may be required at a later date in case of an incompetent bladder neck that has not picked up and treated at initial stage [54]. In 1996, Michael Mitchell [55] described a single‐stage repair technique, where complete penile disassembly is done, and the urethral plate is separated from the glans making the urethral and glans repair independent of each other. Bladder reconstruction is performed at a later stage (usually at five years of age) with a Youngs‐Dees‐Leadbetter procedure. However, some might still be incontinent and require an artificial sphincter. Posterior urethral valve (PUV) is the most common congenital obstructive anomaly of the male urethra. The incidence is between 1 in 5000 to 1 on 8000 male births [56]. Although a few familial cases have been recorded, including in siblings, there is no established genetic predisposition. PUV is a congenital anomaly that is life‐threatening to the foetus. This anomaly is frequently detected by antenatal ultrasound. Its cause is not clearly known. The foetus develops an abnormal insertion of the wolffian ducts into the urogenital sinus leading to a parachute like membrane across the prostatic urethra, exaggerating the folds that normally lead down from the verumontanum, attaching obliquely into the anterior urethra distal to the external urethral sphincter causes a valvelike structure, and obstructing the outflow from the bladder (Figure 30.22). Figure 30.22 Posterior urethral valves. Young first described PUV in 1919. He classified them into three types [4]; however, only type I and III are obstructive. Currently, most of the cases are diagnosed antenatally [4]. Prenatal ultrasound findings are those of high‐pressure chronic retention and include unilateral or bilateral hydronephrosis or hydroureter and thickened bladder with diverticulae and with a dilated posterior urethra giving the so called ‘key‐hole’ appearance. There is also reduced amniotic fluid (oligohydramnios) and varying degrees of renal dysplasia. Postnatally, in addition to the aforementioned findings classically, the posterior urethra is dilated and elongated. Physical findings may include distended, firm bladder, and a weak urinary stream. Abdominal distension as a result of a palpable distended bladder and hydronephrosis (Figure 30.23), urinary ascites, respiratory distress due to pulmonary hypoplasia (due to the oligohydramnios), and stigmata of Potter’s syndrome are seen in severely affected newborns [11]. Figure 30.23 Bilateral dilated ureter behind the bladder. One must remember, that the newborn’s renal function could be normal in the first few days of life as it reflects the mother’s renal function. However, renal deterioration soon ensues. In addition, the hydronephrosis might not be as evident because of the dehydration of the newborn; hence, scans are repeated after one week of birth. Older children present with voiding dysfunctions particularly daytime urge incontinence, voiding, lower urinary tract symptoms, and renal failure. Late cases commonly also present with recurrent UTIs. A series of ‘pop‐off’ or ‘by‐pass’ mechanisms are seen in nearly 20%, whereby a high‐pressure system is reduced, allowing for normal renal development. These include urine leaking intra‐abdominally through a ruptured renal pelvis or even bladder (causing urine ascites), unilateral ureteric reflux which will lead to affected side renal dysplasia while contrary side develops normally (valves, reflux, and dysplasia [VURD] syndrome), and formation of large bladder diverticula. However, the protective value of the pop‐off phenomenon has probably been overstated, and recent evidence suggests that although this may impart some medium‐term benefit, a proportion of boys nevertheless progress to renal failure [57]. Voiding cystourethrogram (VCUG) is diagnostic and demonstrates a dilated elongated posterior urethra with abrupt transition to a narrower distal urethra (Figure 30.24 a and b). Classical findings of VCUG include a distended prostatic urethra, bladder neck hypertrophy, thickened trabeculated bladder with diverticula, and uni‐ or bilateral VUR. Figure 30.24 (a) Cystogram showing dilated posterior urethra and trabeculated bladder. Source: Courtesy Prof Sandesh Parelkar, KEM Hospital, Mumbai India. (b) Cystogram showing dilated posterior urethra, small trabeculated bladder, and bilateral vesicoureteric reflux. Source: Courtesy Prof Sandesh Parelkar, KEM Hospital, Mumbai India Initial postnatal management involves good bladder drainage. This is usually accomplished with 6‐Fr or an 8‐Fr soft feeding tube passed per urethra. Adequate care should be taken to ensure that the tube does not coil within the posterior urethra. Fluid and electrolyte management is critical in the initial period. Postobstructive diuresis needs close monitoring and replacement and are best served in close liaison with paediatric nephrologists. Acid‐base balance is important, more so in severe renal impairment. Prophylactic antibiotics and circumcision at some stage are recommended, especially in children with VUR or dilated upper tract. After initial stabilisation, endoscopic valve ablation or resection is the treatment of choice, either at the 4–5, 7–8, or the preferred 12 o’clock positions. Both Bugbee electrode cauterization and cold knife incision have been described. The most common complication is the formation of urethral stricture disease; however, there is a lower urethral stricture rate by using cold knife as compared to diathermy [4]. In rare cases of small premature babies with raising creatinine levels or where adequate small cystoscopes are not available, it is reasonable to provide higher diversion in the form of Blocksom vesicostomy [11] as a temporary measure. Once the child gains weight and grows up, the valves are ablated endoscopically and the vesicostomy closed. Most centres routinely perform a check cystoscopy few months after primary ablation to ensure completeness of resection and re‐resect any residual valve leaflets. Children with PUV need multidisciplinary close monitoring along with nephrologists in the initial years of life with regular bloods, ultrasound, and baseline functional imaging. A long‐term outcome in children with PUV is dependent on multiple factors. With improvement in the neonatal care along with optimal nephrourological management, the mortality rates have dropped down to 1–3% from 50% in the 1950s [57, 58]. By early adulthood, half will develop chronic renal disease, a third will develop end‐stage renal disease (ESRD) and require renal transplant. Attention to bladder dysfunction and identifying and treating hostile bladders early will delay renal deterioration or protect transplanted kidneys. In bladders that progress to myogenic failure and incomplete emptying, clean intermittent catheterisation with or without overnight drainage may be necessary. Regular follow up with judicious urodynamic assessments of bladder function will identify at‐risk patients before they clinically deteriorate. In adulthood, patients will develop ejaculatory dysfunction, reduced prostatic secretions, and impotence and reduced libido as a result of renal impairment. Foetal intervention for PUV is controversial. Experience with intrauterine valve ablation was reported with enthusiasm and optimism, but no long‐term outcomes are available [57]. Elective preterm delivery is a form of intervention, and it may be beneficial in cases of rapidly progressing late‐onset dilatation [57]. It is important to balance lung maturity with the risk of progressive renal damage in deciding the optimum timing for preterm delivery. Termination of pregnancy is controversial but is considered in some centres, particularly when severe hydronephrosis and oligohydramnios are detected in early pregnancy [57]. In these circumstances, irreversible renal dysplasia is almost invariably present. A multidisciplinary process of decision making involving the parents is vital. Vesico‐amniotic shunting (VAS) is being tried as a temporary diversion in the foetus. The procedure itself carries an appreciable risk of foetal morbidity, which although only 5% in skilled hands is higher (up to 60%) in some published series [57]. The Percutaneous shunting in Lower Urinary Tract Obstruction (PLUTO) study was a randomised controlled trial designed to evaluate clinical effectiveness, cost‐effectiveness, and acceptability of percutaneous VAS for lower urinary tract obstruction. The trial stopped early with 31 women randomised because of difficulties in recruitment. The limited results showed that survival to 28 days and 1 year appears to be higher with VAS than with conservative management, but it is not possible to prove benefit beyond reasonable doubt. Notably, prognosis in both arms for survival and renal function is poor. VAS was substantially costlier and unlikely to be regarded as cost effective based on the one‐year data. Parents should be counselled about the risks of pregnancy loss with or without VAS insertion [59]. Prostatic utricle is a small, blind pouch opening at the verumontanum (Figure 30.25). It is normally lined by glandular epithelium and has no function. It is considered by some to be the male homologue of the female uterus and vagina. However, in 1997, needle aspiration of cysts from the utricles in a series of six patients by Yasumoto et al. demonstrated high levels of prostate‐specific antigen (PSA). And in 2004, Shapirova et al. demonstrated significant concentrations of immunohistochemical bodies to p63 in foetal tissues destined to form the utricle. This points to urogenital origin of the utricle [60, 61]. Figure 30.25 Large prostatic utricle behind the bladder BLD, bladder. Source: Courtesy Prof Sandesh Parelkar, KEM Hospital, Mumbai India. From a practical point of view, it is worth remembering that the utricle is enlarged in up to 10–20% of proximal hypospadias. Some series report an incidence as high as 35–57%. Higher incidence are noted with more severe degrees of hypospadias [41, 42, 62, 63]. This may lead to difficulty in catheterising the bladder per urethra. On occasion, urethral sound or a lacrimal probe or cystoscopy is required to guide the catheter into the bladder. The enlarged prostatic utricles are lined by squamous epithelium and can be symptomatic with UTI, epididymitis, and postvoid dribbling. VCUG, retrograde urethrography, and in some cases, urethroscopy is useful for diagnosis. Enlarged prostatic utricles are classified according to a grading system [52]. Most of the cases are managed conservatively, and only recurrent symptoms warrant surgical excision with high‐risk of injury to vas deference. Syringocele is a rare anomaly of the male urethra. It involves cystic dilatation of the main duct of the Cowper’s glands which can give rise to urethral obstruction or lower urinary tract symptoms like urinary frequency, urgency, dysuria, postvoid incontinence, haematuria, or UTI. Cowper’s glands are located within the levator ani shelf on either side of the membranous urethra. They secrete a mucous substance during ejaculation that acts as a lubricant. The main duct draining Cowper’s glands drain below the urogenital diaphragm into the ventral aspect of the bulbous urethra. Sometimes, these ducts become dilated and infected. The urethrographic appearances then resemble an anterior urethral valve. Cowper’s glands are rarely the site of persistent infection with Neisseria or other organisms. Clinical examination shows a pea‐sized swelling, exquisitely tender, between the layers of the pelvic fascia just anterior to the rectum (Figure 30.26). Figure 30.26 An abscess of Cowper’s gland presents as tender swelling in the pelvic floor felt anterior to the anal canal. Maizels et al. [64] described four types of Cowper’s syringocele: Figure 30.27 Ruptured syringocele. Diagnosis is made by VCUG, retrograde urethrography, or urethrocystoscopy. Treatment is marsupialization of the syringocele. Attempts to remove them are seldom successful or worthwhile; unless the glands are also removed, the ducts will regenerate. Many authors distinguish between anterior urethral valves and diverticula, but others consider them to be one and the same entity as a ruptured syringocele. Anterior urethral valves are composed of folds located on the ventral aspect of the urethra that coapt during voiding, resulting in urethral obstruction. They can be located in the bulbous urethra (40%), penoscrotal junction (30%), and penile urethra (30%). It has been proposed that valves cause proximal urethral dilatation with the formation of a saccular diverticulum or a double‐barrelled urethra (Figure 30.28) [52]. When the boy passes urine, the saccular diverticulum fills out and compresses the normal urethra; hence, the term ‘anterior urethral valve’. Figure 30.28 Anterior urethral valve – a double‐barrelled urethra. Anterior urethral diverticula communicate with the urethra and are found on the ventral aspect of the urethra between the bulbous and mid‐penile urethra. Progressive enlargement of a diverticulum can result in a distal valve‐like flap. Embryologic theories of formation of diverticula include a developmental defect in the corpus spongiosum, cystic dilatation of urethral glands, and sequestration of an epithelial rest. Clinical presentation depends on the patient’s age and the degree of urethral obstruction and includes difficulty voiding, incontinence, and recurrent UTIs. Nonetheless, the clinical history is typical. The child has a poor stream. He strains so hard that ‘he dirties when he wets’. The ballooned second urethra slowly empties, and so the boy seems to be continually incontinent. There is a translucent swelling in the midline. Often this collection of urine becomes infected and the child presents with an abscess which is incised and leaves a permanent fistula. There may be severe upper tract obstruction. They may present in adult life with a stone in the sac. VUR can be found in 20–30% cases. Treatment consists of endoscopic incision of the inferior lip (Figure 30.29). In case of large diverticulum with thin urethral wall, excision of the diverticum and urethroplasty may be need [52]. Figure 30.29 The anterior leaf of the ‘valve’ may be incised endoscopically, but the large diverticula may need repairing later on. Anterior urethral valves in the fossa navicularis, the most distal aspect of the urethra, are referred to as valves of Guerin. Many patients are asymptomatic, and some have been associated with urethral bleeding. VCUG is diagnostic and will demonstrate a small collection of contrast material at the dorsal aspect of the distal urethra. Marsupialization of the valve into the urethral lumen is the treatment of choice. Duplication of the urethra is a rare anomaly (Figure 30.30). Postulated theories include abnormal müllerian duct termination and growth arrest of the urogenital sinus or misalignment of the termination of the cloacal membrane with the genital tubercle. Duplication can be associated with hypospadias, epispadias, cleft lip and palate, congenital heart disease, tracheoesophageal fistula, imperforate anus, and musculoskeletal anomalies. VUR is present in a third of the cases [52]. Figure 30.30 Duplication of the urethra. Duplication commonly occurs along the sagittal plane. The ventral urethra is the more functional urethra and contains the verumontanum and sphincters. When urethral duplication is present along the coronal plane, bladder duplication is always present. Effmann classified urethral duplication into three types: Type I – Partial duplication of the urethra. Type II – Complete duplication of the urethra. IIA1 – both urethrae arise separately from the bladder. IIA2 – one channel arises from the other. Y‐duplication occurs when one urethra arising from the bladder neck or posterior urethra opens to the perineum. This type of urethral duplication often coexists with stenosis of the anterior portion of the normally positioned urethra and other severe congenital anomalies. IIB – duplication with one meatus Type III – Complete duplication of the urethra and bladder. Depending on the type of duplication, patients might be asymptomatic. Symptoms include UTI, epididymitis, and incontinence. VCUG or retrograde urethrography help confirm the diagnosis and delineate the anatomy. Surgical excision of the duplication is mainly reserved for recurrent symptoms. Urethral or bladder neck fistulae to the blind rectal pouch are associated with high or intermediate anorectal malformations in males. Diagnosis is made by VCUG or distal loopogram study following colostomy. Treatment includes the division of the rectal stump close to the urethra (Figure 30.31a and b) and correction of the anorectal anomaly, which is commonly done as a staged operation. Figure 30.31 (a) Rectovesicle fistula. (b) Rectourethral fistula in imperforate anus. Source: Courtesy Prof Sandesh Parelkar, KEM Hospital, Mumbai India. An ambiguous genitalia is a phasing‐out terminology, a general term used to describe any deviation from the normal appearance of the external genitals. The incidence can be as common as 1 in 4500 births. DSD originate from the following underlying mechanisms: A new nomenclature was proposed at the Chicago consensus (2005) and later in 2006, adopted by the Lawson Wilkins Paediatric Endocrine Society (LWPES) and the European Society for Paediatric Endocrinology (ESPE). The new terminology was adopted to reflect advances in our understanding of the pathophysiology of these disorders while being sensitive to the needs and concerns of patients affected by them. Classification and examples: 46, XY DSD (previously male pseudohermaphroditism) 46, XX DSD (previously female pseudohermaphroditism) Sex chromosome DSD Figure 30.32 Females subject to masculinization. Mechanisms causing an excess of androgens. In this, the most common and serious type of DSD, there is some urgency about making the diagnosis because of the risk of a lethal salt‐losing state. CAH (46 XX DSD) account for the majority of DSD, is due to 21‐hydroxylase deficiency (cause of >90% of CAH cases), and leads to virilisation of the female genitalia. It is an autosomal recessive disorder as a result of mutations in chromosome 6. There is an impairment in the production of hydrocortisone, which leads to compensatory increase in ACTH and testosterone production. Characterised in more than 60% by having a ‘salt‐wasting’ aldosterone deficiency (i.e. reduced sodium and chloride with increase in potassium) presenting a few weeks after birth with an adrenal crisis (i.e. severe vomiting and dehydration) and should be recognised because it is a neonatal emergency. Investigations will show an elevation of 17‐OH‐progesterone. This condition is vital to recognise because it will need urgent aggressive rehydration, potassium‐lowering drugs, and steroid replacement with mineralocorticoids and glucocorticoids. Subgroups of CAH include 11B‐hydroxylase deficiency (increased 11‐desoxycortisol: there will be increased sodium and reduced potassium and hypertension) and 3B‐hydroxysteroid dehydrogenase deficiency (increased DHEA and 17‐OH‐pregnoone: salt‐losing disorder). The neuter pattern may fail to become masculine for three main reasons (Figure 30.33): Figure 30.33 Mechanism causing under‐masculinization in males. The most common and severe disorder occurs in testicular feminization, which is a sex‐linked inherited condition. The external genital appearance is female, but the vagina is short. Inguinal hernia are common, and the testicles show Leydig cells are present but no spermatogenesis and there is a considerable risk of forming malignant tumours. The various biochemical investigations may be able to discover whether there is a deficiency of the production of testosterone (from want of 17‐ketosteroid reductase), failure of activation to dihydrotestosterone, or want of the cytosol receptor protein. If the child is reared as a girl, the testicles should be removed to prevent cancer; however, the timing of surgery is decided in the multidisciplinary team meeting. When the syndrome is incomplete, the clitoris may be very large. With the onset of puberty, these children may rapidly virilise. There are a large number of genetic males who are only slightly imperfectly masculinized. Some merely have hypospadias. Others may have persistent müllerian structures and more or less maldescent of the testicles [4]. In these rare chromosomal abnormalities, one gonad may be a testis and the other a ‘streak’ gonad – an ovary without any follicles. Their management calls for great care, and the child should be reared as a boy if there is a well‐developed phallus. Many children with Klinefelter syndrome grow up to be physically quite normal, but their testicles are small, and they are referred because of infertility. More severe cases may be deficient in masculine body hair and require treatment with androgens. The diagnosis is easily made with a buccal smear [5]. In Turner syndrome, the child remains in the neuter–female state. The gonads are streaks of connective tissue in the broad ligaments. There are often associated cardiac defects. The patient is short, with a broad chest and webbed neck [6]. Any suspicion of DSD should prompt a cautious approach with thorough history and physical examination by an experienced paediatric urologist, endocrinologist, geneticists, and psychologists. Assigning gender should be delayed until appropriate tests and further assessments are complete. Centres treating DSD have a multidisciplinary team, including but not limited to, a neonatologist, endocrinologist, geneticist, psychologist, and urologist to plan further investigations and management. A family history should be taken and should include parental lineage, any history of DSD, or genital anomalies, neonatal deaths, primary amenorrhoea or infertility, or any maternal exposure to androgens [4]. The examination should be as equally thorough, focused on determining presence or absence of sexual organs (Figures 30.34 and 30.35). Specialist investigations such as diagnostic laparoscopy (for intra‐abdominal testes), cystoscopy, or hysteroscopy may be required to identify organs. Figure 30.34 Bilateral impalpable testes. Figure 30.35 (a and b) Severe hypospadias with undescended testis on right. Primary investigations include electrolytes, hormonal analysis (human chorionic gonadotropin [HCG] stimulation test, 17‐hydroxyprogesterone, luteinising hormone [LH], follicle‐stimulating hormone [FSH], testosterone, cortisol levels, and ACTH), and karyotyping. Ultrasonography to determine the presence of müllerian duct structures. Investigations are to determine the DSD type; however, the most common occurring DSD is CAH. Determination of the sex of the child should take into consideration the investigations, but also the age of presentation, fertility potential, penile size, presence of a functional vagina, endocrine function, malignancy potential, antenatal testosterone exposure, the child’s appearance, psychosocial well‐being, sociocultural aspect, and parental opinions [4]. Further description of detailed management of each type of DSD is beyond the scope of this chapter. Megalourethra is ectasia of the urethra in the absence of mechanical obstruction. It is caused by defective formation of the penile corpora secondary to a mesodermal defect. Two types of megalourethra are described [52]: Megalourethra is often associated with other congenital abnormalities including cryptorchidism, renal agenesis, hypospadias, primary megaureter, Prune Belly Syndrome, VACTERL complex, and severe gastrointestinal anomalies (Figure 30.36a and b). These patients have a functional rather than anatomic urethral obstruction, causing stasis and back pressure into the upper urinary tracts. Micturating cystourethrogram (MCUG) helps diagnosis. Reconstructive surgery is required. Figure 30.36 (a and b) Prune belly syndrome with megalourethra. Source: Courtesy Prof Sandesh Parelkar, KEM Hospital, Mumbai India. Aphallia or penile agenesis occur secondary to developmental failure of the genital tubercle (Figure 30.37). It is extremely rare and has an incidence of 1 in 10 million to 30 million. The urethra opens into the anal verge or the rectum. Historically, early orchiectomy with female gender reassignment and urogenital reconstruction has been the treatment of choice [66]. In‐utero gender imprinting, the timing and role of gender reassignment, and long‐term psychological effects of gender conversion are ongoing concerns with this approach, and current approaches to management remain controversial [58]. Figure 30.37 Aphallia. Source: Courtesy Prof Sandesh Parelkar, KEM Hospital, Mumbai India. The term ‘microphallus’ or ‘micropenis’ indicates a constitutionally normal penis with a stretched penile length (SPL) more than 2.5 standard deviations (SD) below the mean for age [4]. SPL differentiates the cases with buried appearance of the penis (i.e. obesity or penis concealed by abnormal skin attachments). Endocrine input is essential to identify hypogonadotropic hypogonadism (e.g. Kallmann syndrome or Prader‐Willi syndrome; inadequate secretion of gonadotrophin‐releasing hormone [GnRH]), or hypergonadotrophic hypogonadism (e.g. Gondal dysgenesis; failure of the testes to produce testosterone). Duplication of the penis (diphallia) is another rare anomaly resulting from failure of mesodermal banding. It occurs with a frequency of 1 in 5 million births. Presentation varies from simple accessory penis to complete duplication of the urethra, glans, and corporal bodies. Extent of surgery ranges from simple resection of accessory penis to complex reconstruction, depending on the anatomy of the defect. Penile torsion indicates rotational defect of the phallus and is usually counterclockwise to the left. It may be associated with chordee, hooded prepuce, or hypospadias. Torsion of less than 90° is usually asymptomatic and does not require correction [58]. Surgery when indicated entails complete degloving of the penis to the base with division of dysgenetic fibrous bands. Rarely fixing the base of the corpora to the pubic symphysis or dartos flap is required to maintain corrected position [58].
Penis and Urethra and Prostate Congenital Anomalies
Abstract
30.1 Foreskin
30.1.1 Embryology and Function Review
30.1.2 Phimosis
30.1.3 Circumcision
30.1.3.1 Medical Indications of Circumcision
30.1.3.2 Alternatives to Circumcision
30.1.3.3 Technique of Circumcision
30.1.4 Paraphimosis
30.1.5 Infections and Inflammation of the Foreskin
30.1.5.1 Lichen Sclerosis or Balanitis Xerotica Obliterans
30.1.5.2 Buried Penis and Congenital Megaprepuce
30.2 Hypospadias
30.2.1 Embryology
30.2.2 Incidence, Risk Factors, and Associations
30.2.3 Classification [41, 42]
30.2.4 Diagnosis
30.2.5 Management
30.2.5.1 Penile Curvature
30.2.5.2 Urethral Reconstruction
30.2.5.3 Complications
30.3 Primary Epispadias
30.3.1 Embryology
30.3.2 Types
30.3.3 Presentation
30.3.4 Management
30.4 Posterior Urethral Valves
30.4.1 Embryology
30.4.2 Classification
30.4.3 Clinical Presentation and Diagnosis
30.4.4 Management
30.4.5 Prognosis and Long‐Term Follow‐Up
30.4.6 Indicators of Renal Outcome in PUV [57]
30.4.6.1 Indictors of a Poor Renal Outcome
30.4.6.1.1 Prenatal
30.4.6.1.2 Postnatal
30.4.6.2 Indicators of Good Renal Outcome
30.4.6.3 Role of Foetal Interventions
30.5 Prostatic Utricle
30.6 Syringocele
30.7 Anterior Urethral Valves
30.8 Urethral Duplication
30.9 Urethral Anomalies in Anorectal Malformations
30.9.1 Disorders of Sex Development
30.9.1.1 Nomenclature and Classification [65]
30.9.1.2 Female Subject to Masculinization (46 XX DSD)
30.9.1.3 Congenital Adrenal Hyperplasia (46 XX DSD)
30.9.1.4 Males with Undermasculinisation
30.9.1.5 46, XY DSD
30.9.1.6 Mosaicism (XO/XY)
30.9.1.7 Klinefelter Syndrome (47 XXY)
30.9.1.8 Turner Syndrome (45 XO)
30.9.1.9 Diagnosis
30.10 Interesting Terminologies
30.10.1 Megalourethra
30.10.2 Aphallia
30.10.3 Microphallus
30.10.4 Penile Duplication
30.10.5 Penile Torsion
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